One HPV Vax Dose Might Work as Well as Three

Finding suggests that a key barrier to HPV vaccination might be overcome

Action Points

Note that this post-hoc analysis of previous data suggests that one HPV vaccine administration may confer as much protective immunity as the recommended three doses.

Be aware that women in these trials were not randomized with regard to number of doses, limiting interpretability of these results.

A single dose of the bivalent human papillomavirus (HPV) vaccine appears to give much the same protection as the recommended three doses, researchers are reporting.

The finding, from a post-hoc analysis of two randomized clinical trials, could allow wider use of the vaccine, according to Aimee Kreimer, PhD, of the National Cancer Institute in Bethesda, Md., and colleagues.

HPV type 16 causes about 50% of cervical cancers, the researchers noted, with another 20% caused by HPV-18, so that prevention of infection by the two types could "substantially reduce cervical cancer prevalence and subsequent mortality."

Commercially available vaccines include one that contains HPV-16 and -18 antigens and one that contains antigens from four types -- 6, 11, 16, and 18. Both contain the adjuvant AS04 and have been shown to be highly efficacious in preventing infection by the vaccine types.

But the "costs and infrastructure complexities" of the three-dose schedule are important barriers to vaccination in many places, Kreimer and colleagues noted.

To investigate the issue, they turned to two randomized trials of the bivalent vaccine (Cervarix) -- the Costa Rica Vaccine Trial with 7,466 participants and the PATRICIA study with 18,644.

Both trials randomly assigned women to get the bivalent HPV vaccine or a vaccine against hepatitis A.

In the Costa Rica trial, women who got one, two, or three doses seemed to have uniformly high protection against the vaccine types, a post-hoc analysis suggested. But the numbers were small, so Kreimer and colleagues combined summary data from the study with that from the PATRICIA trial.

In the modified total vaccinated cohort, some 22,327 women got three doses of either HPV or HAV vaccine, 1,185 got two doses, and 543 received one dose. Within each dose category, the proportion getting the active and control vaccines was similar.

The primary endpoint of this analysis was one-time detection of HPV infection.

Four years after vaccination, the analysis showed, vaccine efficacy against infection with HPV-16 and -18 was:

77.0% for 3 doses.

76.0% for 2 doses.

And 85.7% for a single dose.

The researchers also looked at cross-protection against incident infection with HPV-31, -33, and -45 and found that vaccine efficacy for three doses was 59.7%, for two doses was 37.7%, and for one dose was 36.6%.

On the other hand, if the first and second doses were separated by 6 months, the cross-protection was similar to that seen with three doses, they reported.

In the original Costa Rica trial, with a slightly older cohort, there had been a worry that the dose-efficacy findings might have been caused by the vaccination boosting natural immunity caused by previous exposure to the vaccine strains, Kreimer and colleagues noted.

The new analysis showed efficacy regardless of dose in women naive to HPV-16 or -18 infection at the time of vaccination, alleviating those concerns, Kreimer and colleagues reported.

Because of that," they argued, "these results are probably relevant to girls in the preferred age range for HPV vaccination" -- 11 and 12.

The biggest challenge for the authors is that participants were not randomly assigned to the dosage groups, commented Julia Brotherton, BMed, of the National HPV Vaccination Program Register in Melbourne, Australia.

But the data are "very reassuring," she argued in an accompanying editorial, because rates of actual HPV infection with non-vaccine-targeted HPV types were similar.

"Thus confounding or bias does not seem to explain the findings of high efficacy in each dose group," she argued, adding that the finding is also highly plausible with data showing elevated and sustained HPV antibodies even after one dose.

Brotherton also noted the study endpoint is "a high bar for vaccine efficacy estimates" because one-time detection could be either transient deposition from a partner or persistent chronic infection.

That would tend to underestimate the real effect of vaccination, but she noted the researchers also saw a similar signal for persistent infection, which is the preferred outcome measure in HPV vaccine trials.

The studies had support from the National Cancer Institute, the NIH Office of Research on Women's Health, the Ministry of Health of Costa Rica, and GlaxoSmithKline Biologicals SA. Kreimer made no disclosures. Several authors disclosed relevant financial links, including employment and stock ownership, with GSK.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.